Calorie restriction extends yeast life span by lowering the level of NADH
Calorie restriction extends yeast life span by lowering the level of NADH
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DOI：
10.1101/gad.1164804
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发表时间：
2004-01-01
影响因子：
10.5
通讯作者：
Guarente, L
中科院分区：
文献类型：
--
作者：
Lin, SJ;Ford, E;Guarente, L
卡路里限制(CR)可延长多种物种的寿命。在此之前，我们发现热量限制通过激活Sir2来延长酵母的复制寿命，Sir2是一种高度保守的依赖于NAD的脱乙酰酶。在这里，我们测试CR是否通过增加NAD/NADH比率或通过调节已知的Sir2抑制剂烟酰胺的水平来激活Sir2。我们发现CR降低NADH水平，NADH是Sir2的竞争性抑制物。一种特定降低NADH水平的基因干预延长了寿命，验证了NADH调节酵母寿命以响应CR的模型。
Calorie restriction (CR) extends life span in a wide variety of species. Previously, we showed that calorie restriction increases the replicative life span in yeast by activating Sir2, a highly conserved NAD-dependent deacetylase. Here we test whether CR activates Sir2 by increasing the NAD/NADH ratio or by regulating the level of nicotinamide, a known inhibitor of Sir2. We show that CR decreases NADH levels, and that NADH is a competitive inhibitor of Sir2. A genetic intervention that specifically decreases NADH levels increases life span, validating the model that NADH regulates yeast longevity in response to CR.